Analysis of metabolic gases by an implantable cardiac device for the assessment of cardiac output

ABSTRACT

Analysis of metabolic gases by an implantable medical device allows the assessment of the status of a congestive heart failure patient by providing for the assessment of cardiac output. The present invention is directed to an implanted medical device configured to measure concentrations of metabolic gases in the blood to determine cardiac output of a patient. The device is also configured to measure changes in the cardiac output of a patient. The present invention is also directed to a method of measuring cardiac output by an implanted medical device. Further, the detection of changes in cardiac output utilizing an implanted medical device as disclosed herein is useful in a method of detecting exacerbation of congestive heart failure. The implanted medical device can also be used to pace a heart to modify cardiac output in a patient.

PRIORITY CLAIM

This application is a Continuation of U.S. patent application Ser. No.10/938,173 (Attorney Docket No. A04P3021-US1), filed Sep. 10, 2004,which is entitled “Analysis of Metabolic Gases by an Implantable CardiacDevice for the Assessment of Cardiac Output”.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates generally to the field of implantable cardiacdevices, and more particularly, to an implantable cardiac device (ICD)configured to analyze metabolic gases for the assessment of cardiacoutput.

2. Related Art

Many chronic diseases, such as diabetes and heart failure, require closemedical management to reduce morbidity and mortality. Because thedisease status evolves with time, frequent physician follow-upexaminations are often necessary. At follow-up, the physician may makeadjustments to the drug regimen in order to optimize therapy. Thisconventional approach of periodic follow-up is unsatisfactory for somediseases, such as heart failure, in which acute, life-threateningexacerbations can develop between physician follow-up examinations.

Congestive heart failure (CHF) is a chronic disease characterized byfrequent exacerbations leading to expensive hospitalizations. Indeed, apatient hospitalized with CHF has a 50 percent chance of beingreadmitted for the same reason within 6 months. It is well known thatclose, routine monitoring of these patients allows early, simple, andinexpensive medical intervention which can prevent the exacerbation andeliminate the need for hospitalization. Monitoring for signs of animpending exacerbation thus both improves clinical outcomes andsignificantly reduces the cost of caring for these patients. It is wellknown among clinicians that if a developing exacerbation is recognizedearly, it can be easily and inexpensively terminated, typically with amodest increase in oral diuretic. However, if it develops beyond theinitial phase, an acute heart failure exacerbation becomes difficult tocontrol and terminate. Hospitalization in an intensive care unit isoften required. It is during an acute exacerbation of heart failure thatmany patients succumb to the disease.

It is often difficult for patients to subjectively recognize adeveloping exacerbation, despite the presence of numerous physical signsthat would allow a physician to readily detect it. This problem is wellillustrated by G. Guyaft in his article entitled “A 75-Year-Old Man withCongestive Heart Failure,” 1999, JAMA, 281(24): 2321-2328. Furthermore,since exacerbations typically develop over hours to days, evenfrequently scheduled routine follow-up with a physician cannoteffectively detect most developing exacerbations. It is thereforedesirable to have a system that allows the routine, frequent monitoringof patients so that an exacerbation can be recognized early in itscourse. With the patient and/or physician thus notified by themonitoring system of the need for medical intervention, a developingexacerbation can easily and inexpensively be terminated early in itscourse.

The multiplicity of feedback mechanisms that influence cardiacperformance places the heart at the center of a complex control network.The neurohumoral axis includes the autonomic nervous system, consistingof sympathetic and parasympathetic branches, and numerous circulatinghormones such as catacholamines, angiotensin, and aldosterone. Neuralreflex arcs originating from pressure and stretch receptors, whichdirectly measure mechanical hemodynamic status, modulate theneurohumoral axis. Similarly, chemoreceptors respond to changes in CO₂,pH, and O₂, which reflect cardiopulmonary function. The neurohumoralsystem influences cardiac performance at the level of the cardiacelectrical system by regulating heart rate and the conduction velocityof electrical depolarizations. It also influences cardiac performance atthe mechanical level, by controlling contractility, that is, theeffective vigor with which the heart muscle contracts. Conventionalcardiac monitors, such as defibrillators, pacemakers, Holter monitors,and cardiac event records, are tailored for the diagnosis and/or therapyof abnormalities of the cardiac electrical system. In contrast, heartfailure is a disease of the cardiac mechanical system. It is primarily afailure of the myocardium to meet the mechanical pumping demandsrequired of it. In monitoring the status of a heart failure patient,measuring the mechanical hemodynamic variables is desirable. Examples ofmechanical hemodynamic variables include atrial, ventricular, andarterial pressures, and cardiac output (volume of blood pumped into theaorta per unit time).

One approach to frequent monitoring of heart failure patients that hasbeen proposed is the daily acquisition of the patient's weight andresponses to questions about subjective condition (see, for example,Alere DayLink Monitor, Alere Medical, Inc., San Francisco, Calif.). Thesimplicity and noninvasive aspect of this approach are desirablefeatures. However, both the amount and the sophistication of theobjective physiological data that can be acquired in this way are quitelimited, which consequently limits the accuracy of the system.Furthermore, the system requires the active participation of thepatient, who must not deviate from the precise data acquisition routineor risk introducing confounding factors into the acquired data.

In another approach to monitoring cardiac patients, oxygen saturation orpartial pressure sensors are placed in the right ventricle for rateresponsive pacing, in which the pacing rate of the pacemaker iscontrolled based on the metabolic demand of the body, which is a form ofhemodynamic assessment and pace-parameter optimization. Assumingarterial O₂ is constant, a fall in venous O₂ below a critical levelimplies that the cardiac output is not sufficient to meet metabolicdemand. In this case, a pacing parameter, the pacing rate, is increased.

A number of examples of a variety of measures of hemodynamic status,including both implantable embodiments (cardiac output measured usingimpedance plethysmography of the right ventricular volume, and rightventricular pressure) and external embodiments (cardiac output measuredusing Doppler ultrasound, heart sounds, blood pressure, respiratory gasanalysis, and pulse oximetry) are known. External measurements ofhemodynamic status are labor-intensive and can only be used duringperiodic follow-up examination. They are therefore not suitable forarrhythmia discrimination, dynamic pace-parameter optimization,sensitivity optimization, or capture verification.

Non-invasive techniques, such as plethysmography of vasculature, arealso known. These techniques provide the basis of the conventional pulseoximeter, which by using two wavelengths of light, calculates thepercent of arterial hemoglobin that is saturated with oxygen. The lightis typically directed through the fingertip using a temporarily appliedfinger sensor. It can also be directed through other fleshy appendagessuch as the ear and, in infants, the foot. Optical vascularplethysmography also provides the basis for a non-invasive, continuousblood pressure monitor. A cuff containing an optical source and detectoris placed over the finger. The pressure in the cuff is continuouslyvaried so that the amount of light measured at the detector remainsconstant, which indicates that the volume of the vasculature isconstant. In this way the arterial pressure can be inferred from thecuff pressure that is necessary to maintain constant light detection.Thus, while optical plethysmography of the vasculature is known in theart, it has to date been configured mostly for temporary, external use.

What is needed is a technique for continuously measuring cardiac outputsafely and accurately, with minimum disruption to a patient's normalactivities.

SUMMARY OF THE INVENTION

This invention provides for analysis of metabolic gases by a pacemakeror other implantable medical device such as an implantable cardioverterdefibrillator (ICD), or implanted monitor to determine cardiac output toassess the status of a congestive heart failure patient and optimizedevice function. Embodiments of the present invention are directed to animplanted device configured to measure concentrations of metabolic gasesin the blood to determine cardiac output of a patient. The device isalso configured to measure changes in the cardiac output of a patient.The present invention is also directed to a method of measuring cardiacoutput by an implanted device. Further, the detection of changes incardiac output utilizing an implanted device as disclosed herein isuseful in a method of detecting exacerbation of congestive heartfailure. A pacemaker or ICD can also be used to pace a heart to modifycardiac output in a patient.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a simplified diagram illustrating an implantable stimulationdevice in electrical communication with at least three leads implantedinto a patient's heart for delivering multi-chamber stimulation andshock therapy;

FIG. 2 is a functional block diagram of a multi-chamber implantablestimulation device illustrating the basic elements of a stimulationdevice which can provide cardioversion, defibrillation and pacingstimulation in four chambers of the heart.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to an implantable medical deviceconfigured to obtain a measurement of blood gas concentrations, whereinthe blood gas concentrations can be used to estimate cardiac output.Cardiac output can be calculated from blood gas concentrations using theFick equation or an approximation thereof or from a calculation based onthe difference in blood gas concentrations between arterial and venousblood.

For illustration, a particular type of implanted medical device calledan implantable cardioverter defibrillator (ICD) is described. Aconventional ICD can deliver both pacing therapy to treat slow heartrhythms (bradyarrhythmias) and cardioversion or defibrillation therapyto treat fast heart rhythms (tachyarrhythmias). As shown in FIG. 1, anexemplary ICD 10 is in electrical communication with a patient's heart12 by way of three leads, 20, 24 and 30, suitable for deliveringmulti-chamber stimulation and pacing therapy. To sense atrial cardiacsignals and to provide right atrial chamber stimulation therapy, ICD 10is coupled to implantable right atrial lead 20 having at least an atrialtip electrode 22, which typically is implanted in the patient's rightatrial appendage.

To sense left atrial and ventricular cardiac signals and to provideleft-chamber pacing therapy, ICD 10 is coupled to “coronary sinus” lead24 designed for placement in the “coronary sinus region” via thecoronary sinus for positioning a distal electrode adjacent to the leftventricle and/or additional electrode(s) adjacent to the left atrium. Asused herein, the phrase “coronary sinus region” refers to thevasculature of the left ventricle, including any portion of the coronarysinus, great cardiac vein, left marginal vein, left posteriorventricular vein, middle cardiac vein, and/or small cardiac vein or anyother cardiac vein accessible by the coronary sinus.

Accordingly, exemplary coronary sinus lead 24 is designed to receiveatrial and ventricular cardiac signals and to deliver left ventricularpacing therapy using at least a left ventricular tip electrode 26, leftatrial pacing therapy using at least a left atrial ring electrode 27,and shocking therapy using at least a left atrial coil electrode 28.

ICD 10 is also shown in electrical communication with the patient'sheart 12 by way of an implantable right ventricular lead 30 having, inthis embodiment, a right ventricular tip electrode 32, a first, rightventricular O₂ sensor 33, a right ventricular ring electrode 34, a rightventricular (RV) coil electrode 36, and an SVC coil electrode 38.Typically, right ventricular lead 30 is transvenously inserted intoheart 12 so as to place the right ventricular tip electrode 32 in theright ventricular apex so that RV coil electrode 36 will be positionedin the right ventricle and SVC coil electrode 38 will be positioned inthe superior vena cava. Right ventricular lead 30 is capable ofreceiving cardiac signals and delivering stimulation in the form ofpacing and shock therapy to the right ventricle. Right ventricular lead30 is also capable of measuring venous oxygen concentration and sendingthat information back to an electronic circuit contained in ICD 10.

In one embodiment, a second sensor 39 is mounted extravascularly on theexterior housing of ICD 10 for measuring arterial blood gasconcentration. Alternatively it is incorporated within the exteriorhousing or within the header. The output of sensor 39 is coupled to theelectronic circuit contained in ICD 10. The electronic circuit in ICD 10is capable of calculating a measure of cardiac output based on thedifference between arterial and venous blood gas concentrations measuredby sensors 33 and 39.

Except for the addition of right ventricular sensor 33 and extravascularsensor 39, ICD 10 described above is substantially the same as knownICDs, such as are described in commonly owned U.S. Pat. No. 6,658,296B1, to Kenneth Wong, et al., issued Dec. 2, 2003, the disclosure ofwhich is incorporated herein by reference in its entirety as though setforth in full below.

RV sensor 33 may be any of a number of well known sensors, such as areflectance oximetry sensor of the type described, for example, in U.S.Pat. No. 4,807,629, to Michael Baudino et al., issued Feb. 28, 1989, therelevant portions of which are incorporated herein by reference asthough set forth in full below. As is well known, intravascular sensor33 may be configured to measure blood gas concentrations of mixed venousblood.

Extravascular sensor 39 for measuring arterial blood gas concentrationmay be an optical sensor or an electrochemical sensor. Many such sensorsare well known in the art. One example of an extravascular sensor 39 isshown in commonly owned U.S. Pat. No. 6,409,675, to Robert Turcoft,issued Jun. 25, 2002, the disclosure of which is incorporated herein byreference in its entirety as though set forth in full below. An improvedsensor of this type is disclosed in co-pending U.S. application Ser. No.10/764,067 filed Jan. 23, 2004, which is incorporated herein byreference. Sensor 39 may be an O₂ sensor. For example, the O₂ sensor maybe a pulse oximetry sensor.

As illustrated in FIG. 2, a simplified block diagram is shown of themulti-chamber implantable cardiac device 10, which is capable oftreating both fast and slow arrhythmias with stimulation therapy,including cardioversion, defibrillation, and pacing stimulation. While aparticular multi-chamber device is shown, this is for illustrationpurposes only, and one of skill in the art could readily duplicate,eliminate or disable the appropriate circuitry in any desiredcombination to provide a device capable of treating the appropriatechamber(s) with cardioversion, defibrillation and pacing stimulation.

A housing 40 for ICD 10, shown schematically in FIG. 2, is oftenreferred to as the “can”, “case” or “case electrode” and may beprogrammably selected to act as the return electrode for all “unipolar”modes. Housing 40 may further be used as a return electrode alone or incombination with one or more of the coil electrodes, 28, 36 and 38, forshocking purposes. Housing 40 further includes a connector (not shown)having a plurality of terminals, 42, 44, 46, 48, 52, 54, 56, and 58(shown schematically and, for convenience, the names of the electrodesto which they are connected are shown next to the terminals). As such,to achieve right atrial sensing and pacing, the connector includes atleast a right atrial tip terminal (AR TIP) 42 adapted for connection toatrial tip electrode 22.

To achieve left chamber sensing, pacing and shocking, the connectorincludes at least a left ventricular tip terminal (VL TIP) 44, a leftatrial ring terminal (AL RING) 46, and a left atrial shocking terminal(AL COIL) 48, which are adapted for connection to left ventricular ringelectrode 26, left atrial tip electrode 27, and left atrial coilelectrode 28, respectively.

To support right chamber sensing, pacing and shocking, the connectorfurther includes a right ventricular tip terminal (VR TIP) 52, a rightventricular ring terminal (VR RING) 54, a right ventricular shockingterminal (RV COIL) 56, and an SVC shocking terminal (SVC COIL) 58, whichare adapted for connection to right ventricular tip electrode 32, rightventricular ring electrode 34, RV coil electrode 36, and SVC coilelectrode 38, respectively.

At the core of ICD 10 is a programmable microcontroller 60 whichcontrols the various modes of stimulation therapy. As is well known inthe art, microcontroller 60 typically includes a microprocessor, orequivalent control circuitry, designed specifically for controlling thedelivery of stimulation therapy and may further include RAM or ROMmemory, logic and timing circuitry, state machine circuitry, and I/Ocircuitry. Typically, microcontroller 60 includes the ability to processor monitor input signals (data) as controlled by a program code storedin a designated block of memory. The details of the design and operationof microcontroller 60 are not critical to the present invention. Rather,any suitable microcontroller 60 may be used that carries out thefunctions described herein. The use of microprocessor-based controlcircuits for performing timing and data analysis functions are wellknown in the art.

As shown in FIG. 2, an atrial pulse generator 70 and a ventricular pulsegenerator 72 generate pacing stimulation pulses for delivery by rightatrial lead 20, right ventricular lead 30, and/or coronary sinus lead 24via an electrode configuration switch 74. It is understood that in orderto provide stimulation therapy in each of the four chambers of theheart, atrial and ventricular pulse generators 70 and 72 may includededicated, independent pulse generators, multiplexed pulse generators,or shared pulse generators. Pulse generators, 70 and 72, are controlledby microcontroller 60 via appropriate control signals, 76 and 78,respectively, to trigger or inhibit the stimulation pulses.

Microcontroller 60 further includes timing control circuitry 79 which isused to control the timing of such stimulation pulses (e.g., pacingrate, atrio-ventricular (AV) delay, atrial interconduction (A-A) delay,or ventricular interconduction (V-V) delay, etc.) as well as to keeptrack of the timing of refractory periods, PVARP intervals, noisedetection windows, evoked response windows, alert intervals, markerchannel timing, etc., which is well known in the art.

Switch 74 includes a plurality of switches for connecting the desiredelectrodes to the appropriate I/O circuits, thereby providing completeelectrode programmability. Accordingly, switch 74, in response to acontrol signal 80 from microcontroller 60, determines the polarity ofthe stimulation pulses (e.g., unipolar, bipolar, combipolar, etc.) byselectively closing the appropriate combination of switches (not shown)as is known in the art.

Atrial sensing circuits 82 and ventricular sensing circuits 84 may alsobe selectively coupled to right atrial lead 20, coronary sinus lead 24,and right ventricular lead 30, through switch 74 for detecting thepresence of cardiac activity in each of the four chambers of the heart.Accordingly, the atrial (ATR. SENSE) and ventricular (VTR. SENSE)sensing circuits, 82 and 84, may include dedicated sense amplifiers,multiplexed amplifiers, or shared amplifiers. The switch 74 determinesthe “sensing polarity” of the cardiac signal by selectively closing theappropriate switches, as is also known in the art. In this way, theclinician may program the sensing polarity independent of thestimulation polarity.

Each sensing circuit, 82 and 84, preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables ICD 10 to deal effectively with thedifficult problem of sensing the low amplitude signal characteristics ofatrial or ventricular fibrillation. The outputs of atrial andventricular sensing circuits, 82 and 84, are connected tomicrocontroller 60 which, in turn, are able to trigger or inhibit theatrial and ventricular pulse generators, 70 and 72, respectively, in ademand fashion in response to the absence or presence of cardiacactivity in the appropriate chambers of the heart.

For arrhythmia detection, ICD 10 utilizes atrial and ventricular sensingcircuits 82 and 84 to sense cardiac signals to determine whether arhythm is physiologic or pathologic. As used herein “sensing” isreserved for the noting of an electrical signal, and “detection” is theprocessing of these sensed signals and noting the presence of anarrhythmia. The timing intervals between sensed events (e.g., P-waves,R-waves, and depolarization signals associated with fibrillation whichare sometimes referred to as “F-waves” or “Fib-waves”) are thenclassified by microcontroller 60 by comparing them to a predefined ratezone limit (i.e., bradycardia, normal, low rate VT, high rate VT, andfibrillation rate zones) and various other characteristics (e.g., suddenonset, stability, physiologic sensors, and morphology, etc.) in order todetermine the type of remedial therapy that is needed (e.g., bradycardiapacing, anti-tachycardia pacing, cardioversion shocks or defibrillationshocks, collectively referred to as “tiered therapy”).

Cardiac signals are also applied to the inputs of an analog-to-digital(A/D) data acquisition system 90. Data acquisition system 90 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device102. Data acquisition system 90 is coupled to right atrial lead 20,coronary sinus lead 24, and right ventricular lead 30 through switch 74to sample cardiac signals across any pair of desired electrodes.

Microcontroller 60 is further coupled to a memory 94 by a suitabledata/address bus 96, wherein the programmable operating parameters usedby microcontroller 60 are stored and modified, as required, in order tocustomize the operation of ICD 10 to suit the needs of a particularpatient. Such operating parameters define, for example, pacing pulseamplitude, pulse duration, electrode polarity, rate, sensitivity,automatic features, arrhythmia detection criteria, and the amplitude,waveshape and vector of each shocking pulse to be delivered to thepatient's heart 12 within each respective tier of therapy.

Advantageously, the operating parameters of ICD 10 may be non-invasivelyprogrammed into memory 94 through a telemetry circuit 100 in telemetriccommunication with an external device 102, such as a programmer,transtelephonic transceiver, or a diagnostic system analyzer. Thetelemetry circuit 100 is activated by microcontroller 60 by a controlsignal 106. Telemetry circuit 100 advantageously allows intracardiacelectrograms and status information relating to the operation of ICD 10(as contained in microcontroller 60 or memory 94) to be sent to externaldevice 102 through an established communication link 104. In thepreferred embodiment, ICD 10 further includes a physiologic sensor 108,commonly referred to as a “rate-responsive” sensor because it istypically used to adjust pacing stimulation rate according to theexercise state of the patient. However, physiological sensor 108 mayfurther be used to detect changes in cardiac output, changes in thephysiological condition of the heart, or diurnal changes in activity(e.g., detecting sleep and wake states). Accordingly, microcontroller 60responds by adjusting the various pacing parameters (such as rate, AVDelay, V-V Delay, etc.) at which atrial and ventricular pulse generators70 and 72 generate stimulation pulses.

ICD 10 additionally includes a battery 110 which provides operatingpower to all of the circuits shown in FIG. 2. For ICD 10, which employsshocking therapy, battery 110 must be capable of operating at lowcurrent drains for long periods of time (preferably less than 10 μA),and then be capable of providing high-current pulses (for capacitorcharging) when the patient requires a shock pulse (preferably, in excessof 2 A, at voltages above 2 V, for periods of 10 seconds or more).Battery 110 must also have a predictable discharge characteristic sothat elective replacement time can be detected. Accordingly, ICD 10preferably employs lithium/silver vanadium oxide batteries, as is truefor most (if not all) current devices.

ICD 10 further includes a magnet detection circuitry (not shown),coupled to microcontroller 60. It is the purpose of the magnet detectioncircuitry to detect when a magnet is placed over ICD 10, which magnetmay be used by a clinician to perform various test functions of ICD 10and/or to signal microcontroller 60 that external programmer 102 is inplace to receive or transmit data to microcontroller 60 throughtelemetry circuit 100.

As further shown in FIG. 2, ICD 10 is shown as having an impedancemeasuring circuit 112 which is enabled by microcontroller 60 via acontrol signal 114.

Microcontroller 60 includes a cardiac output calculation module 62implemented by computer executable code, firmware, and/or hardware forcalculating cardiac output based on the Fick equation or on thedifference in blood gas concentrations between arterial and venousblood. Microcontroller 60 receives blood gas measurement signals fromsensors 33 and 39. Microcontroller 60 either processes the receivedmeasurement signals internally or stores the measurement signals andtransmits them through telemetry circuit 100 to external device 102 forprocessing. Microcontroller 60 may be capable of calculating an absolutecalibrated value of cardiac output using the Fick equation, or it may beconfigured to calculate an estimate or relative measure of cardiacoutput.

For measuring cardiac output by ICD 10, any metabolic product can beanalyzed, but it is preferable that the analyte is a blood gas, such asO₂ or CO₂.

In one embodiment, telemetry circuit 100 transmits the output of thesensors, including sensors 33 and 39, to a receiver outside the body. Inthis embodiment, the raw data collected by ICD 10 is transmitted to areceiver prior to calculating cardiac output. Cardiac output is thencalculated externally in device 102 as a function of the Fick equation.

In another embodiment, the data is processed internally bymicrocontroller 60 as a function of the Fick equation prior totransmitting a measure of cardiac output to a receiver outside the body.

ICD 10 may also be programmed to adjust at least one pacing parameter inresponse to the cardiac output. Microcontroller 60 determines whetherthe cardiac output requires an adjustment to cardiac pacing. If anadjustment is required, microcontroller 60 sends a signal to theappropriate stimulation electrode for pacing the heart in response tothe measured cardiac output.

The Fick equation is derived below. The derivation is based on oxygenconcentration, but the Fick equation is applicable to any blood gas orblood borne material:

ΔT arbitrary time intervalV_(O2)=net amount of O₂ absorbed by the lungs in time ΔT (L O₂)V_(aO2)=volume of O₂ carried from lungs by systemic arteries in time ΔT(L O₂)V_(vO2)=volume of O₂ carried to lungs by systemic veins in time ΔT (LO₂)C_(aO2)=concentration of O₂ in systemic arterial blood (L O₂/L blood)C_(vO2)=concentration of O₂ in systemic venous blood (L O₂/L blood)V_(blood)=volume of blood carried from or to the lungs in time ΔT (Lblood){dot over (V)}_(O2)=rate at which O₂ is consumed by or delivered to thebody (L O₂/min)CO=cardiac output (L blood/min)S_(aO2)=arterial O₂ saturation: fraction of arterial hemoglobin that isloaded with O2S_(vO2)=venous O₂ saturation: fraction of venous hemoglobin that isloaded with O2[Hb]=concentration of hemoglobin (g/dL blood)1.34=conversion factor relating [Hb] concentration to O2 volume,assuming fully saturated hemoglobin (mL O2/g Hb)

Consider the consumption of oxygen by the body as seen at the level ofthe lungs. In time ΔT, a net volume V_(O2) is inspired by the lungs,which in the steady state is equal to the net amount consumed by thebody. A volume V_(aO2) is delivered to systemic arterial circulation,and a volume V_(vO2) is returned on the venous side.

V _(O2) =V _(aO2) −V _(vO2)  (1)

Expressing the gas volume carried in the blood in terms of theirconcentrations yields:

$\begin{matrix}\left. \begin{matrix}{{V_{{aO}\; 2} = {C_{{aO}\; 2} \cdot V_{blood}}},} \\{V_{{vO}\; 2} = {C_{{vO}\; 2} \cdot V_{blood}}}\end{matrix} \right\} & (2)\end{matrix}$

where V_(blood) is the volume of blood that passes a given point in timeΔT. Since the cardiac output CO is by definition, CO≡stroke volume·heartrate=V_(blood)/ΔT (with equality holding if there is no valvularregurgitation or intracardiac shunt), substituting (2) into (1) anddividing by ΔT gives,

V _(O2) ={C _(aO2) −C _(vO2) }·V _(blood)

V_(O2) /ΔT≡{dot over (V)} _(O2) ={C _(aO2) −C _(vO2) }·V _(blood)/ΔT,  (3)

{dot over (V)} _(O2) ={C _(aO2) ·C _(vO2) }·CO

or,

CO={dot over (V)} _(O2) /{C _(aO2) −C _(vO2)}  (4)

This last result, Eq. (4), is the Fick equation. It can be expressed interms of oxygen saturation, that is, the percentage of hemoglobin thatis loaded with oxygen, using the relation C_(aO2)=(1.34 mL/gHb)·[HbgHb/dL]·SaO2·(10 dL/L)·(L/1000 mL)=0.0134·[Hb]·S_(a)O2 for arterial O2saturation and a similar relation for venous O2 saturation. Eq. (4) thusbecomes

CO={dot over (V)} _(O2)/{0.0134·[Hb]·(S _(a)O2−S _(v)O2)}  (5)

and is expressed in units of L/min.

Other gases or products of metabolism, e.g., CO₂, can be used in placeof O₂. Because most oxygen in the blood is bound to hemoglobin, the Fickequation can be expressed in terms of O₂ saturation and hemoglobinconcentration, as shown above. This is advantageous because it allowscardiac output to be estimated using oxygen saturation sensors. Thederivation assumes steady state. Following an acute change in thesystem, the Fick equation is not valid until steady state has returned,which may require seconds to tens of seconds, or even longer.

ICD 10 or other implantable medical device can be configured to work inconjunction with external equipment or a monitor that measures {dot over(V)}_(O2). Thus, ICD 10 or other device can be configured to obtain anabsolute calibrated value of cardiac output using the Fick equation.However, it is preferable that ICD 10 functions independently inassessing cardiac output in such a way that external equipment, patientcompliance and need for physician interaction is minimized.

In certain embodiments, ICD 10 can utilize the relative difference inoxygen saturation between the arterial and venous blood gasconcentrations to determine cardiac output. This is mathematicallyequivalent to the use of the Fick equation to calculate cardiac outputalthough one advantage is that it is not necessary to measure netinspired O₂ or expired CO₂ as required by the Fick equation, representedas {dot over (V)}_(O2) in Eqs. (4) and (5). The Fick equation relatescardiac output, consumption or production of a substance, anddifferences between arterial and venous concentrations of the substance.It assumes steady state conditions. When the substance is a metabolicgas, the equation requires knowledge of net inspired O₂ or expired CO₂.However, an ICD or other device could approximate the measure ofinspired gas, or treat it as a constant in certain situations. Forexample, when the patient is at rest the baseline metabolic rate can beapproximated based on the patient's size. This allows a good estimate ofcardiac output using Fick equation (4) or (5) and replacing measured{dot over (V)}_(O2) with an approximation. Thus, the cardiac outputmeasurement provided by the ICD or other device need not incorporatemeasured inspired O₂ or expired CO₂. Rather, an approximation of netinspired O₂ or expired CO₂ is used. It should be clear to those of skillin this field that the term can be an absolute measure or it can be aconstant value or an approximation when appropriate. The device cantherefore provide a measurement of cardiac output that is an estimate ofcardiac output. Such a measurement is useful in itself, and can also beused to track changes in relative cardiac output that signal the statusof the CHF patient.

Another simplification of the implementation of Eqs. (4) and (5)involves the recognition that, in the absence of lung pathology, S_(a)O2is nearly always 100% or close to 100%. Thus, in some embodimentsS_(a)O2 is assumed to be constant and data from the extravascular sensor39 is not used, or alternatively, the extravascular sensor is notincluded in ICD 10 or similar implanted device.

Cardiac output derived by application of the Fick equation in animplantable system can be used to automatically optimize the operatingparameters of the system. For example, if the system comprises apacemaker, then measurements of cardiac output can be used to optimizethe atrio-ventricular (AV) pacing interval, also known as the AV delay(AVD), by selecting as the optimum and then using the AVD which producesthe greatest cardiac output. In a specific embodiment the pacemakerdelivers one test AVD for 2-5 minutes, records the cardiac output, thenchanges to another test AVD and repeats the process. Each of a set oftest AVDs is used in random order. After the cardiac output has beenrecorded for each test AVD, the pacemaker selects the test AVD whichproduced the greatest cardiac output as the optimum and then paces withit continuously. Alternatively, the device can perform a numericalanalysis using the set of recorded cardiac outputs in order tointerpolate the optimum AVD from the data. In one specific example, itcalculates the parameters of the best-fitting 3^(rd) degree polynomial,and takes the location of the maximum of the polynomial as the optimumAVD. A similar optimization technique can be performed for theinterventricular pacing intervals in biventricular pacemakers, or ingeneral, for any set of pacing intervals.

In the application of cardiac output to the optimization of pacingintervals, obtaining the absolute calibrated value of cardiac output isnot necessary. In other words, it is not necessary to measure {dot over(V)}_(O2). An absolute calibrated value of cardiac output is notrequired because a measure of cardiac output that allows a relativecomparison of the efficacy of different pacing intervals is sufficient.Because of this, rather than calculating a numerical value of cardiacoutput, as given in the Fick equation, it is sufficient to simply notethe difference in arterial and venous blood concentrations. For example,if the Fick equation is implemented using oxygen saturation, it is thedifference in oxygen saturation between arterial and mixed venous bloodthat is most relevant, not the calibrated value of cardiac output. Sincethe difference appears in the denominator of the Fick equation, smallerdifferences are associated with larger cardiac outputs. Thus, the ICDwould record the O₂ saturation difference associated with each pacinginterval and select as the optimum pacing interval the one whichminimizes the O₂ saturation difference. This is computationally lessintensive than calculating a true cardiac output, and avoids the needfor a proportionality constant, as well as the computation of a divisionoperation. Nevertheless, it is equivalent to performing optimizationbased on cardiac output derived from the Fick equation.

The present invention is also directed to a method of measuring cardiacoutput using an ICD or other implanted medical device. The methodcomprises receiving an arterial blood gas concentration measurement;receiving a venous blood gas concentration measurement; and using thearterial and venous blood gas concentration measurements to determine ameasure of cardiac output. In this aspect of the present invention,receiving an arterial blood gas concentration measurement comprisesreceiving an arterial blood gas measurement from extravascular sensor 39proximate to ICD 10. Receiving a venous blood gas concentrationmeasurement comprises receiving a blood gas concentration measurement inmixed venous blood. Such a measurement comprises receiving a blood gasconcentration measurement from sensor 33 placed in the right ventricleof the heart. As noted above, the blood gas concentration measured is atleast one of O₂ and CO₂ and includes saturation measurements as well asstrict concentration measurements.

In the present method, the data from the blood gas concentrationmeasurements or blood gas saturation measurements is calculated to yielda measure of cardiac output based on the difference in oxygen saturationbetween the arterial and venous blood gas concentrations.

The present invention is also directed to a method of detecting relativechanges in cardiac output using an ICD or other implantable medicaldevice. In this aspect, the method of comprises receiving an arterialblood gas concentration measurement; receiving a venous blood gasconcentration measurement; and using the arterial and venous blood gasconcentration measurements to determine a measure of cardiac output. Thedevice is further configured to detect relative changes in cardiacoutput. Microcontroller 60 calculates cardiac output based on therelative difference in blood gas concentrations, such that over apredetermined time interval the device is capable of detecting changesin cardiac output.

The present invention is also directed to a method of detectingexacerbation of CHF. In this embodiment, ICD 10 can be furtherconfigured to detect an impending exacerbation based on the changesdetected in cardiac output. ICD 10 or other implantable device can beprogrammed to detect the changes in cardiac output that signal animpending exacerbation. Such changes are well known in the art.

The present invention is also directed to a method of pacing a heart tomodify cardiac output using an ICD. This method comprises receiving anarterial blood gas concentration measurement; receiving a venous bloodgas concentration measurement; calculating a measure of cardiac outputusing the arterial and venous blood gas concentration measurements;determining a pacing interval to modify cardiac output; and deliveringan electrical pacing to the heart through a stimulation electrode. Suchpacing can be used to optimize AV or interventricular pacing intervalswherein the cardiac output of the heart is increased by about 10percent. This method can be used to pace the heart to prevent orameliorate exacerbation of CHF.

Having now fully described this invention, it will be understood bythose of skill in the art that the same can be performed within a wideand equivalent range of conditions, formulations, and other parameterswithout affecting the scope of the invention or any embodiment thereof.

1. An implantable cardiac device comprising: an extravascular,extracardiac sensor for measuring arterial blood gas content; anintravascular sensor for measuring venous blood gas content; and anelectronic circuit for providing an indication of cardiac output basedon the difference between said arterial and venous blood gas contents.2. The device of claim 1, wherein said extravascular sensor is mountedon or incorporated on a surface of an exterior housing of the electroniccircuit.
 3. The device of claim 1, wherein said extravascular sensorcomprises an O₂ sensor.
 4. The device of claim 3, wherein saidextravascular sensor is a pulse oximetry sensor.
 5. The device of claim1, wherein said extravascular sensor comprises an electrochemicalsensor.
 6. (canceled)
 7. (canceled)
 8. (canceled)
 9. (canceled)
 10. Thedevice of claim 1, wherein said intravascular sensor is an opticalsensor.
 11. (canceled)
 12. (canceled)
 13. (canceled)
 14. (canceled) 15.(canceled)
 16. (canceled)
 17. A method for deriving an indication ofcardiac output by an implantable cardiac device comprising: (a)measuring an arterial blood gas content extravascularly with animplanted sensor that is positioned outside a patient's heart; (b)measuring a venous blood gas content intravascularly; and (c) deriving ameasure of cardiac output from said measured arterial and venous bloodgas content measurements.
 18. The method of claim 17, furthercomprising: receiving said arterial blood gas content measurement from asensor mounted on or incorporated within a wall of an exterior housingof an electronic circuit of the implantable cardiac device.
 19. Themethod of claim 17, wherein step (a) further comprises measuring saidarterial blood gas content with an O₂ sensor.
 20. The method of claim19, wherein step (a) further comprises measuring said arterial blood gascontent with a pulse oximetry sensor.
 21. The method of claim 19,wherein step (a) further comprises measuring said arterial blood gascontent with an electrochemical sensor.
 22. The method of claim 21,wherein step (a) further comprises measuring said arterial blood gascontent with an electrochemical sensor capable of measuring blood gasesselected from the group consisting of O₂ and CO₂.
 23. The method ofclaim 17, wherein step (b) comprises: performing said measuring step inmixed venous blood.
 24. The method of claim 23, wherein step (b) furthercomprises: performing said measuring step with a sensor placed in theright ventricle of a patient's heart.
 25. (canceled)
 26. (canceled) 27.(canceled)
 28. (canceled)
 29. The method of claim 17, wherein said bloodgas content measures comprise measures of oxygen saturation and whereinstep (c) comprises: calculating a measure of cardiac output based on thedifference in oxygen saturation between said arterial and venous bloodgas contents as a function of the data from said blood gas contentmeasurements of steps (a) and (b).
 30. The method of claim 17, furthercomprising measuring at least one of O₂ and CO₂ as said blood gas.
 31. Amethod of monitoring relative changes in cardiac output by animplantable cardiac device comprising: (a) measuring an arterial bloodgas content extravascularly with an implanted sensor that is positionedoutside a patient's heart; (b) measuring a venous blood gas contentintravascularly; (c) deriving a measure of cardiac output from saidarterial and venous blood gas content measurements to detect relativechanges in cardiac output.
 32. The device of claim 31 wherein thecontent is one of oxygen content and CO₂ content.
 33. The method ofclaim 31, wherein step (a) comprises measuring arterial blood gascontent with a pulse oximetry sensor mounted on or incorporated withinan exterior housing of an electronic circuit of the implantable cardiacdevice.
 34. The method of claim 33, further comprising transforming datameasured by said extravascular pulse oximeter into a measure of cardiacoutput based on the difference in oxygen content between said arterialand venous blood gas content measurements. 35-49. (canceled)